The major goal of this research is the development of mammalian culture systems to test for the mutagenicity of environmental agents. Compounds which are known mutagens are currently being examined for their action in several systems. Both the spontaneous and mutagen induced mutation rate is currently being examined at 3 loci in human lymphoid lines: the hpt locus specifying HGPRT activity; the as locus, specifying argininosuccinate synthetase activity, and the olocus, specifying ouabain resistance. Using murine myeloma cells lines spontaneous and mutagen induced changes in immunoglobulin biosynthesis are being investigated. Emphasis is being placed on the determination of the specific mode of action of mutagens in mammalian cells using two experimental approaches: 1) the structural changes in variant proteins are being determined and 2) systems are being developed which can be specifically reverted by mutagens of certain modes of action. All experiments using the mammalian cells are carried out in parallel in bacterial test systems both to verify the effectiveness of the mutagen and to determine the relationship between mutagenicity in simpler organisms and in more complex, differentiated mammalian cells.